Project 3: Continuous Wave Electron Paramagnetic Resonance Imaging.Summary: Since nitroxides are used as therapeutic agents in vivo in animal models as well as in human applications, monitoring the distribution, metabolism, and elimination, non-invasively is an important goal. This project's main motivation is develop instrumentation and image data collection strategies to provide the capabilities of imaging paramagnetic probes such as the nitroxide radicals, which are not amenable by other means. To accomplish the goals, we have undertaken development of instrumentation as well as novel data acquisition strategies, and the progress on these aspects is given below.Instrumentation:Digital Signal processing in CW EPR imaging: The CW EPR Imaging spectrometer in our laboratory and other labs implements the capability of detecting the paramagnetic species using analog devices. This has been the only option until the advent of digital signal processing (DSP) technology. We have initiated efforts to develop an EPR Spectrometer using DSP technology with hope of realizing significant enhancements in sensitivity of detecting the species of interest. By eliminating analog components, which contribute to noise in general, we have designed, tested and implemented successfully the first EPR spectrometer based on DSP concepts. We are now optimizing the spectrometer and have it ready for routine operation.Rapid-scan EPR imaging: The CW EPR imaging method is an intrinsically slow modality for imaging and therefore is prone to artifacts in in vivo imaging where animal motion such as heart beat, breathing can contribute to noise and image artifacts. We have borrowed concepts developed in NMR Spectroscopy and developed instrumentation for rapid scan capabilities where the scan times have been reduced from several minutes to a few seconds for image. In this mode of image data collection, individual projections which make the image take less than millisecond minimizing motional artifacts. The first version of the scanner is complete and we also introduced an efficient way of image data collection by rotating the gradients. Initial feasibility studies are complete and currently, we are optimizing the scanner for automated operation.Co-axial coil for EPR Imaging: Current studies in animals in EPR Imaging require us to have the animal placed in a resonator coil which is perpendicular to the magnet axis for signal detection. However, this makes causes difficulty in monitoring the vital signs, maintain core body temperature, maintain anesthesia and have i.v lines in the animal for contrast agent delivery. A resonator coil co-axial with the magnet axis avoids these difficulties. We have tested a resonator coil which satisfies this need and compared with the previous versions. We have found that we are able to carry out in vivo experiments with great ease and also realized enhanced sensitivity in detection.T1-weighted imaging for pO2 mapping: EPR spectra of paramagnetic species are prone to an artifact called "power saturation" where signal intensity is lost at higher RF powers, especially in regions where the oxygen-dependent line width is significantly lower than when in the presence of normoxic conditions. Utilizing this artifact, we have developed a novel image data collection/image reconstruction procedure where it was possible to collect image data rapidly compared to currently used methods and obtain quantitative maps of pO2.